Corticomotoneuronal function in asymptomatic SOD-1 mutation carriers

Abstract

Objective: Diffusion tensor imaging (DTI) recently identified structural abnormalities of corticomotoneurons in asymptomatic copper/zinc superoxide-dismutase-1 (SOD-1) gene mutation carriers. The potential existence of longstanding corticomotoneuronal dysfunction would clearly have consequences for the medical management of asymptomatic SOD-1 mutation carriers. To clarify this unexpected finding, DTI techniques were combined with threshold tracking transcranial magnetic stimulation (TMS) to assess the anatomical and functional integrity of corticomotoneurons in asymptomatic SOD-1 mutation carriers.

Methods: TMS studies were undertaken using a 90 mm circular coil on seven asymptomatic SOD-1 mutation carriers and results were compared to 62 healthy controls. DTI studies were carried out using a 3T magnetic resonance device in the same asymptomatic SOD-1 mutation carriers. Results were compared to age-matched healthy controls.

Results: In contrast to previous findings, there were no significant differences in fractional anisotropy (SOD-1 mutation carriers, 0.62+/-0.01; controls, 0.61+/-0.02, P=0.2) and trace apparent diffusion coefficient (SOD-1 mutation carriers, 0.003+/-0.0001; controls, 0.003+/-0.0001) in asymptomatic SOD-1 mutation carriers. Of further relevance, there were no significant differences in short-interval intracortical inhibition (SOD-1 mutation carriers, 7.9+/-3.4%; controls, 8.5+/-1.1%, P=0.26), intracortical facilitation (P=0.5), MEP amplitude (P=0.44), resting motor threshold (P=0.36) and cortical silent period duration (P=0.29).

Conclusions: Combined anatomical and functional modalities established normal integrity of corticomotoneurons in asymptomatic SOD-1 mutation carrier subjects.

Significance: Additional factors other than simply SOD-1 mutation expression are required to trigger cortical hyperexcitability and neurodegeneration in FALS.